This study investigated effects of resveratrol on Aβ levels in AD Tg mice. Mitochondrial dysfunction and oxidative stress have been implicated in multiple neurodegenerative diseases including Alzheimer’s disease (AD), and the changes can be plausibly linked to plaque and tangle formation. Furthermore, Aβ by itself is capable of producing free radicals and ROS. The extensive data that supports an important role of oxidative stress in neurodegenerative disorders concomitantly support the beneficial effect of antioxidants as adjunctive or supportive therapy. Resveratrol possesses a wide range of biological effects that include anti-oxidative, anti-inflammatory and anti-carcinogenic properties. In vitro studies suggest that resveratrol may protect against β-amyloid induced oxidative cell damage and may promote Aβ clearance through promotion of intracellular proteosomal activity. Recent studies show that resveratrol increases longevity and delays the onset of aging in a manner similar to that of caloric restriction. In this study, mice were fed clinically feasible dosages of resveratrol for forty-five days. Neither resveratrol nor its conjugated metabolites were detectable in brain. Nevertheless, resveratrol diminished plaque formation in a region specific manner. The changes occurred without detectable activation of SIRT-1 or alterations in APP processing. However, brain glutathione declined 21% and brain cysteine increased 54%, which may be linked to the diminished plaque formation. This study supports the concept that onset of neurodegenerative disease may be delayed or mitigated with use of dietary chemo-preventive agents that protect against β-amyloid induced neuronal damage.